Blood Cells - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 138

is promoted by interleukin-4 and -25 via STAT6 factor. The expression of GATA3
is upregulated by IL4, T-cell receptor, Notch, and Wnt signalings [ 252 ].
T H2 cells operate via their production of type-2 cytokines (IL4, IL5, IL9, IL13,
and IL25) and homing to specific tissues. T H2 cells control immunity against
extracellular parasites and allergic responses. Epithelial and dendritic cells and
basophils sense allergens and helminth products and initiate T H2 -type immune
responses [ 252 ]. During the initiation stage of T H2 -cell development, epithelial
cells produce T H2 -promoting cytokines, such as thymic stromal lymphopoietin and
interleukin-25 and -33, and basophils manufacture TSLP, IL4, and IL25. Dendritic
cells and basophils can serve as T H2 -inducing antigen-presenting cells.
During sensitization to allergen, activated allergen-specific CD4 + helper-2

T cells produce T H2 cytokines that trigger a switch to -immunoglobulin heavy

chain and IgE production by B cells via IL4 [ 253 ]. Immunoglobulin-E stimulates
mastocytes and basophils by binding to high-affinity IgE Fc

R1 receptor. The

allergen-IgE-Fc R1 complex provokes degranulation of mastocytes and basophils,

thereby releasing heparin, histamine, serotonin, leukotrienes, prostaglandins, pepti-
dases, chemokines, and cytokines that prime the immediate phase of the allergic
reaction with smooth myocyte constriction, edema that results from vascular
permeability, and inflammatory cell recruitment. Immunoglobulin-E also binds to
Fc R2

of B cells. Allergen uptake by antigen-presenting cells and subsequent presentation
of allergen-derived peptides to specific CD4

R1 of dendritic cells and monocytes, as well as low-affinity IgE receptor Fc

+ T cells lead to the late phase of the

allergic reaction.
T H2 cells migrate to lungs, where they recruit eosinophils via IL5 and mastocytes
via IL9 [ 252 ]. Moreover, they act on epithelial cells via IL4, IL9, and IL13
and smooth myocytes via IL4 and IL13 to cause mucus production, goblet cell
metaplasia, and airway hyperresponsiveness. Type-2 cytokines also target T cells
via IL4, IL9, and IL25, macrophages via IL4 and IL13, as well as IL5- and/or
IL13-producing, non-B, non-T cells via IL25 [ 252 ]. Furthermore, T H2 cells produce
amphiregulin of the epidermal growth factor family and IL24, in addition to IL2,
IL10, and IL21 [ 252 ].

T H9 Cell

Interleukin-9 targets B and T lymphocytes, mastocytes, as well as erythroid
progenitors. CD4 , IL9-producing T cells constitute a subset distinct from other

types of helper T cells.
T H9 cells depend on transforming growth factor-

+

β ,IL4,andIL25[ 254 ]. Agents

TGF and IL4 render T cells IL25-responsive, as they stimulate IL17Rb expression.

Factor TGF

β

reprograms T H2 cells so that they switch their synthesis from T H2
cytokines to IL9 and IL10. Interleukin-25 does not initiate T H9 polarization from
naive CD4

β

T cells. Interleukin-25 operates via both IL17Ra and IL17Rb that
promote the production of IL4, IL5, and IL13. Interleukin-25 provokes IL9 and
IL10 production in differentiated T H9 cells. In fact, IL25 promotes IL9 expression
independently of IL4, but dependently on TGF

+

β .